TY - JOUR
T1 - Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM
AU - Wong, Sandy
AU - Hamidi, Habib
AU - Costa, Luciano J.
AU - Bekri, Selma
AU - Neparidze, Natalia
AU - Vij, Ravi
AU - Nielsen, Tina G.
AU - Raval, Aparna
AU - Sareen, Rajan
AU - Wassner-Fritsch, Elisabeth
AU - Cho, Hearn J.
N1 - Funding Information:
GO29695 was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of HC and HH, was provided by Helen Cathro, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd. We would like to thank the Mount Sinai Human Immune Monitoring Core (HIMC) team, especially Bhaskar Upadhyaya for his expertise and assistance with the CyTOF data, Hui Xie for the execution of the Olink assay, and Seunghee Kim-Schulze for her expertise and management of the assays.
Funding Information:
GO29695 was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of HC and HH, was provided by Helen Cathro, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd. We would like to thank the Mount Sinai Human Immune Monitoring Core (HIMC) team, especially Bhaskar Upadhyaya for his expertise and assistance with the CyTOF data, Hui Xie for the execution of the Olink assay, and Seunghee Kim-Schulze for her expertise and management of the assays.
Publisher Copyright:
Copyright © 2023 Wong, Hamidi, Costa, Bekri, Neparidze, Vij, Nielsen, Raval, Sareen, Wassner-Fritsch and Cho.
PY - 2023
Y1 - 2023
N2 - Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.
AB - Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.
KW - atezolizumab
KW - biomarkers
KW - daratumumab
KW - multiple myeloma
KW - tumor microenvironment, multi-omics
UR - http://www.scopus.com/inward/record.url?scp=85167349166&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1085893
DO - 10.3389/fimmu.2023.1085893
M3 - Article
C2 - 37559718
AN - SCOPUS:85167349166
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1085893
ER -